Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013224 | SCV001173780 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-07 | criteria provided, single submitter | clinical testing | The p.S6F variant (also known as c.17C>T), located in coding exon 1 of the BRIP1 gene, results from a C to T substitution at nucleotide position 17. The serine at codon 6 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001071716 | SCV001237034 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2019-12-29 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRIP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 6 of the BRIP1 protein (p.Ser6Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. |